Carrageenan-induced inflammation in rat pleural cavity was used as a model to study how cellular activity is altered by anti-inflammatory drugs during the inflammatory response. In the early stages of the response, the pleural exudate contained large numbers of intact basophils and had high levels of histamine which were located almost entirely in the cells. At later stages, the histamine content and basophil count decreased and the exudate consisted largely of neutrophils. Pretreatment with H1 and H2 antihistaminic drugs produced a partial (42%) reduction in fluid volume, as did pretreatment with the histamine liberator compound 48/80. Anti-inflammatory drugs, in pharmacological doses, produced a marked decrease in volume (63-73%) as well as in the number of cells mobilized. The histamine content of total exudate was not significantly altered by this treatment. These results suggest that histamine plays only a minor role in this form of inflammation and that the major effect of treatment with anti-inflammatory drugs is a reduction in volume and the number of cells mobilized.